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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endometriosis, a debilitating disease associated with infertility, is characterized by the prolonged presence of ectopic endometrial tissue and the involvement of activated peritoneal fluid macrophages. Apoptosis, which occurs in both endometrium and peritoneal fluid macrophages, is controlled in part by members of the Bcl-2/Bax family of proteins. Here, through immunohistochemical staining, we investigated the Bcl-2/Bax status in endometrium and peritoneal fluid macrophages in endometriosis. Bcl-2/Bax immunoreactivity was found predominantly in the glandular epithelial cells, mainly during the proliferative phase of the menstrual cycle for Bcl-2 but throughout the entire menstrual cycle for Bax. Ectopic endometrium contained a population of Bcl-2 positive. Bax negative tissue macrophages. Fluorescence-activated cell sorting of isolated peritoneal fluid macrophages showed that women with endometriosis had a significantly higher proportion of Bcl-2 positive macrophages than the non-endometriotic group. The proportion of Bax positive peritoneal fluid macrophages was significantly elevated in women without endometriosis. The increased proportion of Bcl-2 positive macrophages found in women with endometriosis may predispose these cells to resist apoptosis. The continued survival of these active cells could have important consequences for the survival and proliferation of the ectopic endometrial tissue.
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PMID:Immunolocalization of the apoptosis regulating proteins Bcl-2 and Bax in human endometrium and isolated peritoneal fluid macrophages in endometriosis. 904 20

Apoptosis research has accelerated with the discovery of genes within a common cell death pathway and evidence for their inter-relationship. Breakthroughs include insights into the mechanism of action of the Bcl-2 family, caspases and their targets, and death receptor complexes. Deregulation of apoptosis is evident in tumors and viral infection, as well as in autoimmune disease, immunodeficiency, neurodegeneration, and infertility.
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PMID:Errors of homeostasis and deregulated apoptosis. 938 73

Although the study of germ cell death is arguably still in its infancy as a field, several recent breakthroughs have provided the fodder for a story, replete with episodes of apparent mass cellular suicide if not murder, that will undoubtedly serve as a research base for many laboratories over the next several years. Death is known to strike the male and female germlines with roughly equal intensity, but the innate feature of male germ cells being self-renewing while those of the female are not places the death of oocytes in a completely different light. Indeed, the functional life span of the female gonads is defined in most species, including humans, by the size and rate of depletion of the precious endowment of oocytes enclosed within follicles in the ovaries at birth. This continuous loss of oocytes throughout life, referred to by many as the female biological clock, appears to be driven by a genetic program of cell death that is composed of players and pathways conserved from worms to humans. It is on this genetic pathway, and the role of its constituent molecules in regulating female germ cell fate, that this review will focus. Emphasis will be placed on those studies using genetic-null or transgenic models to explore the functional requirement of proteins, such as Bcl-2 family members, Apaf-1, and caspases in vertebrates to CED-9, CED-4, and CED-3 in Caenorhabditis elegans, in oocyte survival and death. Furthermore, hypotheses regarding the potential impact of translating what is now known of the oocyte death pathway into new approaches for the clinical diagnosis and management of female infertility and the menopause will be offered as a means to stimulate further research in this new and exciting field.
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PMID:Oocyte apoptosis: like sand through an hourglass. 1045 43

Studies into the mechanisms underlying spermatogenesis, the process by which spermatogonia undergo meiosis to become spermatozoa, have identified a number of genetic determinants of male infertility. Indeed, a more comprehensive knowledge of the genetic regulation of spermatogenesis has alleviated the dependence on the use of idiopathic infertility as a classification for sterile men for whom a cause for their infertility is unknown, as genetic factors become more accountable for this phenotype. This review focuses on selected areas implicated in male infertility including: (i) autosomal and sex chromosomal abnormalities; (ii) genetic disorders associated with impaired gonadotrophin secretion or action; (iii) microdeletions within regions of the Y-chromosome containing candidate gene families for spermatogenesis; (iv) the genetic nexus between cystic fibrosis and congenital bilateral absence of the vas deferens; and (v) insights into human infertility as gleaned from animal studies into mechanisms involving the Bcl-2 family of apoptosis regulators and the interaction between the c-kit encoded tyrosine kinase receptor and its ligand, stem cell factor. As significant advances continue to further knowledge of the genetic basis of male infertility, such as those leading to an understanding of the aforementioned areas, greater progress can be made to rectify or at least ameliorate social stigmas associated with sterility.
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PMID:Selected genetic factors associated with male infertility. 1209 33

Apoptosis is necessary for the development and maturation of Leydig cells. However, increased apoptosis results the decline of testosterone production, which may increase germ cell apoptosis and the possibility of infertility. There are several aspects contributing to Leydig cell apoptosis such as ethane dimethanesulphonate (EDS), glucocorticoid, developmental stage and some hormones including FSH, LH/hCG and testosterone. A number of genes are involved in the regulation of Leydig cells apoptosis. It was reported that SCF/c-kit, Bcl-2 and Bcl-xl inhibited the apoptosis while caspase-3, Fas, Bax and clusterine stimulated it.
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PMID:[Leydig cell apoptosis and its regulation]. 1286 41

Since the cloning of the bcl-2 gene in 1985, considerable progress has been made in elucidating the function of Bcl-2 and related proteins in controlling apoptosis. Although much of this work initially relied on the ectopic expression of bcl-2 gene family members in cell lines in vitro, a number of genetically manipulated mice have been generated to better understand the in vivo significance of specific family members to organ development and homeostasis. Of the many tissues that exhibit apoptosis at some point during fetal or postnatal life, the female gonads arguably possess one of the highest and most protracted incidences of apoptosis, associated with development and maturation of the germ line. Moreover, female germ cells (oocytes) are, for as-yet poorly understood reasons, extremely vulnerable to a host of pathological insults, such as anti-cancer therapies, that ultimately cause premature ovarian failure and infertility due to accelerated oocyte death. Accordingly, efforts to understand the occurrence and regulation of apoptosis in the ovary are of considerable importance from both biological and clinical perspectives. This review will highlight what is known of apoptosis in the female gonads, and the role that Bcl-2 family members play in regulating this process.
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PMID:Current concepts in Bcl-2 family member regulation of female germ cell development and survival. 1499 4

Apoptosis has been shown to be an important regulator of endometrial function during the menstrual cycle and implantation. Recently, some possible implantation defects were identified in patients with unexplained infertility. In this study, we investigated the role of spontaneous apoptosis, which is regulated by death regulatory genes, such as Bcl-2, Bax, p53, and isoenzymes of nitric oxide synthases; eNOS and iNOS during the implantation window in women with unexplained infertility. Endometrial samples were evaluated from fertile (n=15) and unexplained-infertile women (n=15) during post-ovulatory 7th or 8th day of their menstrual cycles. Apoptotic cells were detected using the dUTP nick-end labelling assay and Bcl-2, Bax, p53, iNOS and eNOS were assessed immunohistochemically. Reduced apoptotic cells, weak immunoreactivity of p53 and strong immunoreactivity of Bcl-2 were observed in the unexplained-infertile group compared with the fertile group (p<0.001). Bax intensity was similar in both groups. While weak iNOS immunoreactivity was detected in both groups, moderately increased eNOS immunoreactivity was observed in infertile cases. Spontaneous apoptosis is reduced in the endometrium of unexplained-infertile women, and is associated with the changed Bcl-2:Bax ratio. This finding may be a contributing factor to defective implantation causing infertility in this group of patients.
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PMID:Changed Bcl:Bax ratio in endometrium of patients with unexplained infertility. 1613 38

Apoptosis is a process of cell suicide, the mechanisms of which are encoded in the chromosomes of all nucleated cells. Apoptosis occurs spontaneously throughout mammalian spermatogenesis for the development of normal mature spermatozoa and for the elimination of excess or abnormal germ cells: a critical prerequisite for functional spermatogenesis under physiological conditions. Any deregulation of the apoptotic process during spermatogenesis would lead to defective sperm formation and while increased apoptosis could potentially lead to infertility, decreased cell death could do the same by disrupting testicular homeostasis due to accumulation of cells. Male germ cell apoptosis occurs through two major pathways, involving either mitochondria (intrinsic) or cell surface death receptors (extrinsic). The mitochondrial pathway of apoptosis involves the Bcl-2 group of proteins and different members of this group are involved in diverse situations. The cell death receptor pathway involves members of the TNF receptor superfamily. The stimuli for germ cell apoptosis are internal cues that control proper homeostasis of the testicular tissue or external agents including testicular toxins, heat stress and chemotherapeutic agents. In addition, an imbalance of hormones can lead to the apoptosis of germ cells. The pathway of apoptosis adopted by the germ cells depends on the type of stimuli they receive. This review discusses the recent advances made in the understanding of the mechanisms of germ cell apoptosis that may provide clues to the control of male fertility or treating germ cell tumors and other testis associated pathological conditions.
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PMID:Modulators of spermatogenic cell survival. 1756 72

It is believed that the endowment of primordial follicles in mammalian ovaries is finite. Once follicles are depleted, infertility ensues. Thus, the size of the initial endowment has consequences for fertility and reproductive longevity. Follicular endowment is comprised of various processes that culminate with the incorporation of meiosis-arrested oocytes into primordial follicles. Apoptosis is prominent during follicular endowment, and apoptosis regulatory genes are involved in its regulation. Conflicting data exist with regard to the role of the proapoptotic Bcl-2 associated X protein (BAX) in follicular endowment. Therefore, we investigated the role of BAX during follicular endowment in embryonic and neonatal ovaries. We found that BAX is involved in regulating follicular endowment in mice. Deletion of Bax yields increased oocyte numbers in embryonic ovaries and increased follicle numbers in neonatal ovaries when compared with wild-type ovaries. Increased follicular endowment in Bax -/- ovaries is not due to enhanced germ cell viability. Further, it is not due to an increased primordial germ cell (PGC) allotment, a delay in the onset of meiosis, or altered proliferative activity of oogonia. Instead, our data suggest that the regulatory activity of BAX in follicular endowment likely occurs during PGC migration, prior to PGC colonization of the gonad.
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PMID:BAX regulates follicular endowment in mice. 1761 17

Endometriosis is defined as the presence of ectopic endometrial-like tissue outside the uterus cavity. This disease, afflicting women during their reproductive age, is mainly associated with pelvic pain and infertility. Sampson's theory which supports the ability of endometrial fragments from retrograde menstruations to slough through fallopian tubes and reach peritoneal environment has been recognized as the most plausible explanation for endometriosis during many years. However, further studies provided evidence that fundamental abnormal changes may occur within the eutopic endometrium of women with endometriosis compared to that of women without endometriosis. These dysfunctions included genetic predisposition, genes aberrantly expressed such as matrix metalloproteinases, Hox genes, integrins, anti-apoptotic genes Bcl-2, but also steroid hormones, immuno-inflammatory factors and angiogenesis. This review aims at summarizing and emphasizing a non exhaustive panel of biochemical and molecular factors abnormally expressed in the eutopic endometrium and related to the pathogenesis of endometriosis.
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PMID:Insights into endometriosis-associated endometrial dysfunctions: a review. 1948 56


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